Male Fertility Depends On Intensity Of (sperm) Metabolism

Discussion in 'Scientific Studies' started by haidut, Dec 12, 2019.

  1. haidut

    haidut Member

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    Yet another aspect of health that turns out to be directly controlled by quality/speed of metabolism. I made a few posts in the past demonstrating that progesterone and pregnenolone activate a calcium channel (CatSper) specific to progesterone, which greatly increases sperm motility.

    Progesterone activates the principal Ca2+ channel of human sperm
    https://www.sciencedaily.com/releas...cedaily.com/releases/2016/03/160317150803.htm

    However, I suspected that this is not the whole story behind sperm motility and that energy is somehow involved since increased motility increases energetic demands. The effects of progesterone on increasing metabolism further suggested such metabolic principle is involved but until now there was no direct evidence. The study below fills in this gap and demonstrates that sperm motility directly depends on sperm cell metabolic intensity. Considering estrogen blocks the activation of CatSper by progesterone/pregnenolone, these recent findings also implicate estrogen in yet another pathology affecting massive numbers of people worldwide and part of the benefit of progesterone/pregnenolone exert is likely also due to their opposition to estrogen, especially in the gonads as another recent post discussed.

    Pregnenolone (P5) Fully Prevents Testicular Atrophy Due To Steroid (ab)use Or High Estrogen

    Interestingly, other steroids including cortisol and even testosterone (in high dose) were also found to block the CatSper channel, which easily explains why stress leads to infertility and why clinical trials with testosterone for male infertility have mostly failed. Even more intriguing is that various terpenoids widely distributed in the plant kingdom were also found to block that channel, which could explain the striking prevalence of infertility among male vegans.

    Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids. - PubMed - NCBI

    "...The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that (i) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and (ii) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization."

    "...However, coadministration of testosterone and P4 to spermatozoa, which were preexposed to testosterone, completely prevented ICatSper potentiation by P4 (Fig. 1 A and B and Table S1). Estradiol (E2) and hydrocortisone (HC) partially reduced CatSper activation by P4 to 3.6- and 4.1-fold, when applied simultaneously with P4 (Fig. 1 C and D and Table S1). "

    Furthermore, since up to 25% of couples are directly or functionally infertile, the study below serves as another striking reminder of just how poor the metabolic health of the general population is. It also suggests direct measures that can be taken to improve male fertility including (the obvious) progesterone/pregnenolone supplementation due to their direct effect on sperm, as well as other pro-metabolic measures such as thyroid, magnesium, vitamin E, salt, protein, sugar, etc.

    The motility-based swim-up technique separates bull sperm based on differences in metabolic rates and tail length
    https://phys.org/news/2019-11-biologists-sperm-quality-basis-metabolism.html

    "...Thanks to the advanced possibilities, in vitro fertilization is part of everyday medical practice. The so-called swim-up method is a sperm purification method that is being used daily in andrology labs around the world as a simple step for in vitro sperm selection. This method accumulates the most motile sperm in the upper fraction and leaves sperm with low or no motility in the lower fraction by adding them to a culture medium. The reasons for the different sperm qualities are still poorly understood. A team of biologists from TU Dresden has now compared bovine sperm from the upper and lower layers with regard to their metabolic rate, their motility and sperm tail length. In their study, they identified clear connections: the faster sperm selected by swim-up show higher metabolic rates and longer driving flagella than non-selected cells. The results of the study are the first to provide a metabolic explanation for why the swim-up method selects sperm that appear to be functionally superior. These findings can be applied to all human and animal sperm and provide valuable new insights into the origins of life."
     
  2. Cleo

    Cleo Member

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    Very interesting.

    Does anyone know how to test male fertility? Like, signs of high/low fertility?

    I know, for women it is rather easy because one can track and feel ovulation occurring (right?).
     
  3. Experienced

    Experienced Member

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    Function In Men
    Luteinizing hormone stimulates Leydig cells in the testes to produce testosterone. If testosterone levels decrease, LH secretion increases. This is known as negative feedback.

    Testosterone, in turn, stimulates sperm production as well as generating male characteristics throughout the body [1].

    Luteinizing Hormone Test
    An LH test measures the amount of Luteinizing Hormone in the sample of blood or urine. It may be done to find the cause of a couple’s inability to become pregnant. LH test is commonly used to evaluate [3, 4]:

    • A woman’s egg supply (ovarian reserve)
    • A man’s sperm count
    • Menstrual problems in women.
    • A women’s response to medicines taken to stimulate ovulation.
    Normal Range
    Depending on the sex, phase of the cycle, and other factors, normal LH blood levels may vary [5, 6]:

    • women in the follicular phase of the menstrual cycle: 1.9 to 12.5 IU/L
    • women at the peak of the menstrual cycle: 8.7 to 76.3 IU/L
    • women in the luteal phase of the menstrual cycle: 0.5 to 16.9 IU/L
    • pregnant women: less than 1.5 IU/L
    • women past menopause: 15.9 to 54.0 IU/L
    • women using contraceptives: 0.7 to 5.6 IU/L
    • men between the ages of 20 and 70: 0.7 to 7.9 IU/L
    • men over 70: 3.1 to 34.0 IU/L
    Low Luteinizing Hormone
    LH levels are a marker of reproductive health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it.

    Luteinizing hormone (LH) deficiency is uncommon on its own; LH deficiency almost always occurs with follicle-stimulating hormone (FSH) deficiency because these hormones are secreted by the same sets of cells [7, 8].

    Signs & Symptoms
    • Irregular or absent menstrual periods (in women) [9]
    • Loss of body and facial hair (in men) [10]
    • Erectile dysfunction and/or decreased libido (in men) [10]
    • Infertility in both women and men [1, 11]
    Potential Causes
    • Hypopituitarism [12]
    • Hypogonadism [13, 14]
    • Delayed puberty [15]
    • Kallmann’s syndrome [16] – caused by a deficiency in gonadotropin-releasing hormone (i.e., LHRH). It can result in a lack of sexual development, a small penis, undeveloped testes, and a delay in or lack of puberty [16].
    Other:
    • Smoking cigarettes and marijuana [17, 18]
    • Vitamin D deficiency [19, 20, 21]
    • Tumors in the pituitary gland [22]
    • Digoxin (Lanoxin or Digox) treatment [23]

      High Luteinizing Hormone
      LH levels are a marker of reproductive health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it.

      High luteinizing hormone (LH) levels may cause fertility problems. Some women with high LH have lower rates of fertilization and pregnancy [1].

      In men, high levels may indicate testicular failure and infertility [32].

      High LH levels are seen in genetic conditions such as Klinefelter’s syndrome. It shrinks the testes and causes them to not produce enough testosterone [33].
    Associated Conditions
    In postmenopausal women, an increase in LH levels may play a role in Alzheimer’s Disease development. LH has been shown to promote the deposition of amyloid β plaques in the hippocampus, as seen in Alzheimer’s [34].

    Signs & Symptoms
    • Absent or irregular menstrual cycles (in women) [35]
    • Infertility in both women and men [36, 11]
    Potential Causes
    • Polycystic ovary syndrome (PCOS) [37, 9]
    • Early (precocious) puberty [38]
    • Genetic abnormalities (mutations in the luteinizing hormone/chorionic gonadotropin receptor that cause ambiguous genitalia and infertility) [39]
    • Tumors in ovaries [40]
    • Thyroid disorders [41]
    Testicular failure can also cause high luteinizing hormone levels. This can be caused by:

    • Thyroid disorders [42]
    • Viral infections [43]
    • Tumors [44]
    • Radiation [45]
    • Radiation therapy [46]
    • Chromosomal disorders, such as Klinefelter syndrome [47]
     
  4. JKX

    JKX Member

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    From a purely observation point of view, and trying not to be too crude (!), the volume of semen in the ejaculate would be a pretty good marker of reproductive health.
     
  5. OP
    haidut

    haidut Member

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    Total testosterone (T) levels, combined with prolactin are perhaps the best predictors of male fertility. It has been known since the 1960s that a male with T levels in the bottom 25% has very difficult time begetting children and raising T levels to the upper 25% usually resolves that problem. Prolactin should be in the lower 50% of the normal range, as some people can have high T levels (maybe due to supplementation) but if prolactin levels are elevated then fertility will suffer. Prolactin is a good infertility biomarker in both men and women and this is why drugs like bromocriptine are commonly used in infertile people (mostly women as male prolactin is rarely checked), while for males androgens like T and Proviron are used. Males also benefit greatly from bromocriptine.
    The effect of mesterolone on sperm count, on serum follicle stimulating hormone, luteinizing hormone, plasma testosterone and outcome in idiopathic oligospermic men - PubMed

    In addition, progesterone supplementation is also likely to help as sperm motility depends on progesterone.
    Male Fertility Requires Progesterone And Antagonism Of A PUFA Metabolite
     
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